Paper of the Month - July 2025
selected by the BMAS Scientific Board

Superstable lipid vacuoles endow cartilage with its shape and biomechanics

Raul Ramos1,2, Kim T Pham1,2, Richard C Prince3,4, Leith B Leiser-Miller5, Maneeshi S Prasad6,7, Xiaojie Wang1,2, Rachel C Nordberg4, Benjamin J Bielajew4, Jerry C Hu4, Kosuke Yamaga1,2, Ji Won Oh1,2,8,9,10, Tao Peng11,12, Rupsa Datta4, Aksana Astrowskaja13, Axel A Almet11,14, John T Burns1,   2, Yuchen Liu1,2, Christian Fernando Guerrero-Juarez1,2,11,12, Bryant Q Tran1,2 , Yi-Lin Chu1,2, Anh M Nguyen1,2, Tsai-Ching Hsi1,2, Norman T-L Lim15, Sandra Schoeniger16,17, Ruiqi Liu1,2, Yun-Ling Pai2,18, Chella K Vadivel2,19, Sandy Ingleby20 , Andrew E McKechnie21,22, Frank van Breukelen23, Kyle L Hoehn24, John J Rasweiler 4th25, Michinori Kohara26 , William J Loughry27, Scott H Weldy28, Raymond Cosper29, Chao-Chun Yang30,31 , Sung-Jan Lin18, Kimberly L Cooper32, Sharlene E Santana5,33, Jeffrey E Bradley33, Michael A Kiebish3, Michelle Digman12,35, David E James36, Amy E Merrill37, Qing Nie11,12,14, Thomas F Schilling1,12,14, Aliaksandr A Astrowski38, Eric O Potma3, Martín I García-Castro6, Kyriacos A Athanasiou4, Richard R Behringer39, Maksim V Plikus1,2,12,14

Affiliations: 1Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.2Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA. 3Department of Chemistry, University of California, Irvine, Irvine, CA, USA.4 Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, USA.5Department of Biology, University of Washington, Seattle, WA, USA. 6Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA, USA.7Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.8Department of Anatomy, College of Medicine, Yonsei University, Seoul, Republic of Korea. 9Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. 10Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Republic of Korea.11Department of Mathematics, University of California, Irvine, Irvine, CA, USA. 12Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, USA. 13Scientific Research Laboratory of Molecular Medicine, Grodna State Medical University, Grodna, Belarus.14NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA, USA. 15National Institute of Education, Singapore, Republic of Singapore.16Institute of Veterinary Pathology, Leipzig University, Leipzig, Germany. 17Discovery Life Sciences Biomarker Services GmbH, Kassel, Germany. 18Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan. 19LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. 20Australian Museum, Sydney, NSW, Australia. 21Mammal Research Institute, Department of Zoology and Entomology, University of Pretoria, Hatfield, South Africa. 22South African National Biodiversity Institute, Pretoria, South Africa. 23School of Life Sciences, University of Nevada, Las Vegas, Las Vegas, NV, USA. 24School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia. 25Department of Obstetrics and Gynecology, SUNY Downstate Medical Center, New York, NY, USA. 26Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. 27Valdosta State University, Valdosta, GA, USA. 28Serrano Animal and Bird Hospital, Lake Forest, CA, USA. 29Santa Ana Zoo, Santa Ana, CA, USA. 30Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 31International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan. 32Department of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA. 33Department of Mammalogy, Burke Museum, University of Washington, Seattle, WA, USA. 34BPGbio, Inc., Framingham, MA, USA. 35Department of Chemical Engineering and Materials Science, University of California, Irvine, Irvine, CA, USA. 36Charles Perkins Centre, School of Life and Environmental Sciences and School of Medical Sciences, University of Sydney, Sydney, NSW, Australia.37Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA. 38The Institute of Biochemistry of Biologically Active Compounds, Grodna, Belarus. 39Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Correspondence: Maksim V Plikus, plikus@uci.edu

Science 2025 Jan 10; 387(6730):eads9960
 

Abstract

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis. Consequently, lipochondrocytes grew uniform lipid droplets that resisted systemic lipid surges and did not enlarge upon obesity. Lipochondrocytes also lacked lipid mobilization factors, which enabled exceptional vacuole stability and protected cartilage from shrinking upon starvation. Lipid droplets modulated lipocartilage biomechanics by decreasing the tissue’s stiffness, strength, and resilience. Lipochondrocytes were found in multiple mammals, including humans, but not in nonmammalian tetrapods. Thus, analogous to bubble wrap, superstable lipid vacuoles confer skeletal tissue with cartilage-like properties without “packing foam–like” extracellular matrix.

Graphical Abstract

Graphical abstract from Ramos (2025) Science 10 Jan 2025 Vol 387, Issue 6730

Lipid-filled cartilage of mammals. Unlike in conventional cartilage, the form and function of lipid-filled cartilage derives from giant lipid vacuoles (center). Vacuolated cartilage in mammals represents convergent evolution with the notochord, which has cells containing giant aqueous vacuoles. Developing cartilage grows vacuoles by a tightly controlled biochemical pathway (bottom). Mature lipocartilage maintains stable vacuoles by turning off lipid mobilization. This unusual molecular biology safeguards the vacuoles from unintended size fluctuations upon systemic metabolic disturbances. ECM, extracellular matrix.

Copyright © 2025 the authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original US government works.